Preventing Postoperative Relapse in Crohn's Disease Patients at Risk: Azathioprine Versus Mesalazine

Crohn's Disease Clinical Trial

Official title:

Double-blind, Double-dummy, Randomised, Multicentre, Comparative Study on the Efficacy and Safety of Azathioprine Versus Mesalazine for Prevention of Clinical Relapses in Crohn's Disease Patients With Postoperative Moderate or Severe Endoscopic Recurrence

Clinical Trial Details — Status: Completed

Administrative data

• NCT number: NCT00946946
• Other study ID #: AZT-2/CDP
• Status: Completed
• Phase: Phase 3
• First received: July 24, 2009
• Last updated: June 25, 2012
• Start date: February 2002
• Est. completion date: July 2009

Study information

• Verified date: June 2012
• Source: Dr. Falk Pharma GmbH
• Contact: n/a
• Is FDA regulated: No
• Health authority: Germany: Federal Institute for Drugs and Medical Devices
• Study type: Interventional

Clinical Trial Summary

This study aims to compare azathioprine versus mesalazine tablets for the prevention of clinical relapse in postoperative Crohn's disease (CD) patients with moderate or severe endoscopic recurrence.

Recruitment information / eligibility

• Status: Completed
• Enrollment: 78
• Est. completion date: July 2009
• Est. primary completion date: May 2007
• Accepts healthy volunteers: No
• Gender: Both
• Age group: 18 Years to 70 Years

Eligibility

Inclusion Criteria:

• Signed informed consent,

• Man or woman between 18 and 70 years of age,

• Diagnosis of Crohn's disease confirmed by endoscopic and histological, or endoscopic and radiological criteria within one year or by histopathological criteria during resection,

• Clinical remission defined as Crohn´s Disease Activity Index (CDAI) < 200, within the last two weeks. No clinical relapse due to Crohn's disease since resection,

• Moderate (i2a) or severe endoscopic recurrence (i3-i4) within 6 to 24 months after curative resection of the terminal ileum and partial colectomy with ileocolonic resection for complications of ileal Crohn´s disease and with a construction of an ileocolonic anastomosis,

• Within the neoterminal ileum at least more than 5 aphthous lesions with normal mucosa between the lesions, or skip areas of larger lesions,

• Negative pregnancy test at screening visit in females of childbearing potential,

• Use of appropriate contraceptive methods for females of childbearing potential and males with procreative capacity during treatment and at least up to 3 months after the end of treatment.

Exclusion Criteria:

• Lesions confined to the ileocolonic anastomosis (i.e., < 1 cm in length)

• Short bowel syndrome,

• Serious secondary illnesses of an acute or chronic nature, which in the opinion of the Investigator renders the patient unsuitable for inclusion into the study,

• Serum creatinine levels exceeding 1.5 mg/dL or 130 umol/L,

• Presence of an ileo-/colonic stoma,

• Genotype: thiopurine methyltransferase (TPMT) -/-,

• Known previous or concurrent malignancy (other than that considered surgically cured, with no evidence for recurrence for 5 years),

• Treatment with cytostatics or immunosuppressants, methotrexate, cyclosporine, 6-MP, Azathioprine, 6-TG or anti-TFN-alpha therapy since resection; postoperative treatment with corticosteroids for more than 4 weeks or postoperative treatment with oral antibiotics (e.g., metronidazole, ciprofloxacin) for more than 4 weeks,

• Application of non-steroidal anti-inflammatory drugs (NSAIDS) within 2 weeks before Screening visit except low dose acetylsalicylic acid and except paracetamol,

• Known intolerance/hypersensitivity to study drugs or drugs of similar chemical structure or pharmacological profile,

• Scheduled or intended active immunisation with living vaccines within the next 12 months,

• Well-founded doubt about the patient's cooperation,

• Existing pregnancy, lactation, or intended pregnancy or impregnation within the next 15 months,

• Non-use of appropriate contraceptives in males with procreative capacity and females of childbearing potential (e.g. condoms for males, intrauterine device [IUD], hormonal contraception for females, or a means of contraception for a particular patient considered adequate by the responsible investigator) during treatment and within 3 months after the end of treatment,

• Participation in another clinical trial within the last 30 days, simultaneous participation in another clinical trial, or previous participation in this trial,

• Present stricture plasty (no exclusion if the present stricture plasty was macroscopically without any relevant finding of inflammation seen during index surgery.

Study Design

Allocation: Randomized, Endpoint Classification: Efficacy Study, Intervention Model: Parallel Assignment, Masking: Double Blind (Subject, Caregiver, Investigator, Outcomes Assessor), Primary Purpose: Prevention

Related Conditions & MeSH terms

• Crohn Disease
• Crohn's Disease

Intervention

Drug:
• Azathioprine
2.0-2.5mg/kg/BW azathioprine /day and mesalazine placebo tablets
• Mesalazine
4g Mesalazine tablets/day AND azathioprine placebo tablets
• Azathioprine placebo
4g Mesalazine tablets/day AND azathioprine placebo tablets
• Mesalazine placebo
2.0-2.5mg/kg/BW azathioprine /day and mesalazine placebo tablets

Locations

Country	Name	City	State
Austria	Universitaetsklinik für Innere Medizin III, Abteilung Gastroenterologie and Hepatologie	Vienna
Germany	Robert-Bosch Krankenhaus, Innere Medizin I	Stuttgart

Sponsors (1)

Lead Sponsor	Collaborator
Dr. Falk Pharma GmbH

Countries where clinical trial is conducted

Austria,  Germany, 

References & Publications (1)

Reinisch W, Angelberger S, Petritsch W, Shonova O, Lukas M, Bar-Meir S, Teml A, Schaeffeler E, Schwab M, Dilger K, Greinwald R, Mueller R, Stange EF, Herrlinger KR; International AZT-2 Study Group. Azathioprine versus mesalazine for prevention of postoper — View Citation

Outcome

Type	Measure	Description	Time frame	Safety issue
Primary	The primary endpoint was therapeutic failure at one year, defined as CDAI score =200 and an increase of =60 points from baseline, or study drug discontinuation due to lack of efficacy or intolerable adverse drug reaction.		12 months	Yes
Secondary	endoscopic improvement at month 12, defined as =1 point reduction in Rutgeerts' score.		12 months	No
Secondary	change in CDAI score		12 months	No
Secondary	adverse events		12 months	Yes